Local tolerability of two low-molecular-weight heparins, nadroparin and enoxaparin

  • S Mathijs University of Pretoria
  • J J van Tonder Triclinium Clinical Development (Pty) Ltd
  • J M Dippenaar University of Pretoria
Keywords: low molecular weight heparin, injection site reaction, tolerability, pain, nadroparin, enoxaparin, oedema, haematoma, bruising


Subcutaneous administration of low-molecular-weight heparins is associated with localised injection site reactions such as acute pain, bruising, induration, and haematomas. Repeated exposure to such painful procedures may adversely affect treatment compliance.

The aim of this clinical trial was to assess local administration site tolerability, specifically pain intensity, after a single subcutaneous injection of two common low-molecular-weight heparins, nadroparin and enoxaparin, as compared to placebo.

A five-week, double-blind, placebo-controlled, single-centre, cross-over, phase IV trial was conducted in 15 healthy volunteers. Following a screening period, participants received a single sequence of subcutaneous injections of nadroparin calcium, enoxaparin sodium and sodium chloride 0.9% w/v (placebo) at each of three visits, after which a final safety follow-up visit was conducted. The primary outcome measurement was subjective acute pain measured using visual analogue and numeric rating scales.

Subjective pain at the injection site was significantly greater following enoxaparin injection, as compared to both nadroparin and placebo. Both enoxaparin and nadroparin administration resulted in more severe erythema, haematoma and oedema, as compared to placebo. As expected, only a few adverse events were reported, all of which were mild and resolved spontaneously.

Nadroparin presents favourable injection site tolerability in terms of reduced pain intensity and duration. Tolerability associated with different treatments, especially in terms of pain, is an important consideration at prescription because of its effect on patient adherence to treatment and ultimately the effectiveness of treatment.

Author Biographies

S Mathijs, University of Pretoria

Department of Pharmacology, University of Pretoria, South Africa

J J van Tonder, Triclinium Clinical Development (Pty) Ltd

Triclinium Clinical Development (Pty) Ltd, South Africa

J M Dippenaar, University of Pretoria

3Department Maxillo-Facial-Oral-Surgery, Oral and Dental Health Hospital, University of Pretoria, South Africa